Non-phosphorylatable cyclin D1 mutant potentiates endometrial hyperplasia and drives carcinoma with Pten loss

Cyclin D1 is a regulatory subunit of cyclin-Dependent Kinases 4 and 6 (CDK4/6) and regulates progression from G1 to S phase of the cell cycle. Dysregulated cyclin D1-CDK4/6 contributes to tumor development. Enforced expression of non-phosphorylatable cyclin D1T286A mutant, frequently observed in human cancers, drives tumorigenesis. However, physiological functions of cyclin D1T286A is unclear. We have generated a conditional knock-in mouse model where cyclin D1T286A is expressed under the control of its endogenous promoter, permitting us to study the precise functions of cyclin D1T286A in tumorigenesis. The expression of cyclin D1T286A from its endogenous promoter induces inflammation-mediated lymphocyte disorder and mesenteric tumor formation. Uterine-specific expression of cyclin D1T286A accelerates Pten loss driven endometrial hyperplasia to promote uterine cancer. Examiniation of gene expression profiles. Total RNA was extracted for RNA seq from mouse embryonic fibroblasts. Treatmets are as follows